September 4, 2017
Apellis Pharmaceuticals issued results of a phase II study of APL-2 in patients with geographic atrophy (GA) associated with age-related macular degeneration (AMD). The FILLY trial was a 246-patient, phase II, multicenter, randomized, single-masked, sham-controlled clinical trial of APL-2 in patients with GA conducted at 40 clinical sites in the U.S., Australia and New Zealand. APL-2 was administered as an intravitreal injection in the study eye monthly or every other month for 12 months, followed by six months of monitoring after the end of treatment. Eyes were evaluated for GA by fundus autofluorescence photographs (FAF). The rate of GA area growth was measured by mean change in square root area of GA lesion from baseline to month 12. The primary endpoint was the change in GA lesion size from baseline to month 12, compared to sham. At 12 months, APL-2, administered monthly via intravitreal injection, showed a 29% (p=0.008) reduction in the rate of GA lesion growth compared to sham. With every other month administration, a 20% (p=0.067) reduction was observed. Additionally, in a post hoc analysis, a greater effect was observed during the second six months of the study: a reduction in growth rate of 47% (p<0.001) with monthly administration, and a reduction of 33% (p=0.01) with every other month administration. Phase III studies are planned.
August 21, 2017
Ophthotech announced that the pre-specified primary endpoint of mean change in visual acuity at 12 months was not achieved in its phase III clinical trial investigating Fovista (pegpleranib) anti-PDGF therapy in combination with Eylea (aflibercept) or Avastin (bevacizumab) anti-VEGF therapy compared to Eylea or Avastin monotherapy for the treatment of wet age-related macular degeneration (AMD). The addition of 1.5mg of Fovista to an Eylea or Avastin regimen did not result in benefit as measured by the mean change in visual acuity at the 12-month time point. This clinical trial (also known as OPH1004) was an international, multicenter, randomized, double-masked, controlled study. In the OPH1004 trial, subjects receiving Fovista in combination with Eylea or Avastin therapy gained a mean of 9.42 letters of vision on the ETDRS standardized chart at 12 months, compared to a mean gain of 9.04 ETDRS letters in patients receiving Eylea or Avastin monotherapy, a resulting difference of 0.38 ETDRS letters (p=0.74). The results for the pre-specified primary efficacy analysis were not statistically significant. In addition, the company did not observe any clinically meaningful visual benefit in the pre-specified secondary endpoints when Fovista was added to Eylea or Avastin regimen. Based on these data, the company has decided to stop treating patients who are in the second year of the OPH1004 study. The phase III trial enrolled approximately 640 patients with wet AMD.
June 27, 2016
Acucela, a clinical-stage ophthalmology company that specializes in identifying and developing novel therapeutics to treat and slow the progression of sight-threatening ophthalmic diseases, announced today top-line results from the phase IIb/III clinical trial (S.E.A.T.T.L.E. study) of the investigational visual cycle modulator emixustat hydrochloride (emixustat). “We are carefully reviewing the data in geographic atrophy before we decide on our next steps with emixustat in this indication. We will continue to advance our in-licensed projects as well as our in-house research.” The study enrolled 508 patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The study did not meet its primary endpoint with none of the treatment groups showing a significant difference in lesion growth rate from placebo. The lesion growth rates over 24 months for the 10mg, 5mg, 2.5mg and placebo groups were 1.84 mm2/year, 1.83 mm2/year, 1.69 mm2/year, 1.69 mm2/year, respectively. There was no significant difference in the mean change of best corrected visual acuity from baseline to month 24 between treatment groups. There was a small numerical treatment difference observed in certain patients with specific genetic profiles in favor of emixustat.
April 13, 2015
Ohr Pharmaceutical issued results of a
phase II trial of OHR-102 (0.2% squalamine
lactate ophthalmic solution) combination
therapy for the treatment of the wet form of
age-related macular degeneration (wet-AMD).
The study was a nine-month trial enrolling 142
subjects with two treatment arms—OHR-102
drops administered twice daily plus Lucentis
PRN v. placebo eye drops administered twice
daily plus Lucentis PRN. In the intent-to-treat
population with classic containing choroidal
neovascularization (CNV) (OHR-102 n=38,
Lucentis monotherapy n=32), 42% of the
patients receiving OHR-102 achieved a =3
line gain at nine months, as compared to 28%
in the Lucentis monotherapy group. Less of
a benefit was seen in the overall population
(classic containing and occult only CNV lesions).
In patients with classic CNV, mean gains
in visual acuity were +10.5 letters for the OHR-
102 combination arm and +5.4 letters with
Lucentis monotherapy, a clinically meaningful
benefit of +5.1 letters. The mean number of
injections between the treatment arms, the
primary endpoint of the study, was not meaningfully
different. OHR-102 was generally well-tolerated,
with only two treatment-related
discontinuations in the study. These analyses
will help guide and optimize the design of the
phase III trials of OHR-102 in wet-AMD.
July 28, 2014
Molecular Partners issued results of a
phase II study of DARPin abicipar pegol for
wet age-related macular degeneration (AMD).
In stage three of the phase II, double-masked
study, 64 patients were randomized to abicipar
pegol 1mg (n=25), abicipar pegol 2mg (n=23)
or ranibizumab 0.5mg (n=16) and were followed
for 20 weeks. All patients received doses
at the start of the trial and at four and eight
weeks. Patients in the ranibizumab arm of the
study received additional doses at 12 and 16
weeks. Patients who were treated with either
dose of abicipar pegol received sham injections
at 12 and 16 weeks. Topline data showed
after 16 weeks, mean visual acuity improvement
from baseline was 8.2 letters for abicipar
pegol 2mg, 6.3 letters for abicipar pegol 1mg
and 5.3 letters for ranibizumab. After 20 weeks
(12 weeks after the last abicipar injection
and four weeks after the last ranibizumab
injection), mean visual acuity improvement
from baseline was 9 letters for abicipar pegol
2mg, 7.1 letters for abicipar pegol 1mg, and
4.7 letters for ranibizumab. In addition, Optical
Coherence Tomography (OCT) data was supportive
of the visual acuity data.
September 9, 2013
Roche reported results of a phase II trial of lampalizumab for the treatment of advanced dry age-related macular degeneration (AMD). The multi-center, randomized, single-masked, controlled study in patients with geographic atrophy (GA) associated with AMD. Study participants received lampalizumab injections in one eye either monthly or every other month for 18 months. The primary endpoint was change of GA area from baseline to month 18 compared with control, as assessed with fundus autofluorescence (FAF). Lampalizumab showed a 20.4% reduction rate in the area of GA at 18 months (p<0.1170, statistically significant per pre-specified protocol criteria) in patients. The efficacy assessed by FAF was observed in those receiving monthly injections beginning at month six and maintained through month 18. There was no apparent treatment effect observed in the all-comer every other month dosing group. In a specific sub-population of GA patients treated monthly with lampalizumab that was identified using exploratory biomarkers, the GA progression rate was decreased by 44% (p<0.005) at 18 months. In the subset of patients positive for the exploratory biomarkers who presented with better vision (20/50 to 20/100), progression of the GA area was reduced by 54% (p<0.005) at 18 months when treated with monthly lampalizumab. From the patient samples collected in the MAHALO study, 57% were positive for the exploratory biomarkers.
June 18, 2012
Ophthotech released results from a phase IIb trial of Fovista for the treatment of neovascular age-related macular degeneration (wet AMD). This randomized, controlled, combination trial enrolled 449 patients. Subjects received Fovista 0.3mg in combination with Lucentis 0.5mg; Fovista 1.5mg in combination with Lucentis 0.5mg; or sham in combination with Lucentis 0.5mg every four weeks for 24 weeks. Subjects receiving Fovista 1.5mg and Lucentis gained a mean of 10.6 letters of vision on the ETDRS standardized chart at 24 weeks, compared to 6.5 letters for patients receiving Lucentis monotherapy (p≡0.019), representing a 62% additional benefit. An average absolute benefit of 7.4% over Lucentis monotherapy was present across all ETDRS lines of vision gain. The drug was well tolerated and no significant safety concerns were observed. Based on these results, Ophthotech plans to expedite the preparation of a phase III registration program.
December 5, 2011
Acucela issued results from a phase Ia and Ib trial of ACU-4429 for the treatment of dry age-related macular degeneration. The phase Ia single-center, randomized, double-masked, placebo-controlled, dose-escalation study trial enrolled healthy subjects aged 55 to 80 years. A single dose, oral administration of ACU-4429 was well-tolerated and a dose-dependent modulation of the visual cycle was demonstrated using electroretinography. The phase Ib trial enrolled 40 healthy subjects aged 26 to 55 years. The subjects received daily doses of ACU-4429 for 14 days. ACU-4429 was well tolerated at doses up to 40 mg per day.
November 29, 2010
Regeneron and Bayer reported interim results from two phase III trials of VEGF Trap-Eye for the treatment of neovascular age-related macular degeneration. These two-year, identical, randomized, double-masked, non-inferiority trials were dubbed VIEW 1 and VIEW-2 (VEGF Trap: Investigation of Efficacy and safety in Wet age-related macular degeneration). VIEW-1 enrolled 1,217 subjects in North America while VIEW-2 enrolled 1,240 subjects across international sites. The studies were designed to compare VEGF Trap-Eye to ranibizumab (Lucentis). VEGF Trap-Eye was administered at doses of 0.5 mg or 2.0 mg at four-week dosing intervals or 2.0 mg at an eight-week dosing intervals while ranibizumab was administered at 0.5 mg every four weeks. The primary endpoint was the proportion of subjects treated with the VEGF Trap-Eye who maintain or improve vision at the end of one year, compared to ranibizumab. Visual acuity was determined by the scores on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The primary endpoint was reached in both trials. In VIEW-1 96%, 95% and 95% of subjects who received VEGF Trap-Eye 0.5mg monthly, 2mg monthly and 2mg bi-monthly, respectively, achieved maintenance of vision compared to 94% of subjects receiving ranibizumab. In VIEW-2 96% of subjects in all VEGF Trap-Eye dose groups achieved maintenance of vision compared to 94% of subjects receiving ranibizumab.
September 6, 2010
ReVision Therapeutics released positive results from a phase IIb trial of fenretinide for the treatment of geographic atrophy (GA). This double-masked, placebo-controlled trial enrolled 246 subjects who were randomized to receive once-daily oral doses of 100 mg or 300 mg of fenretinide or placebo for 24 months. At two years, 15 of 82 subjects (18.3%) in the placebo arm progressed to choroidal neovascularization (CNV), while 15 of 164 subjects (9.2%) in both fenretinide arms developed CNV. Analysis of GA lesion growth by color fundus photography showed a trend for slowing of lesion growth in subjects receiving fenretinide; the clearest results were seen in the 300 mg dose group. Fenretinide was well tolerated with no severe drug-related adverse events and no significant effects on normal vision function.
ThromboGenics issued positive results from a phase III trial evaluating microplasmin for the non-surgical treatment of vitreomacular adhesion (VMA). This randomized, placebo controlled, double blind trial (TG-MV-007) enrolled 326 subjects with focal VMA who received a 125ug microplasmin intravitreal injection or placebo injection. The primary endpoint was the proportion of subjects with non-surgical resolution of focal vitreomacular adhesion at day 28. Of the subjects who received microplasmin, 25.3% achieved resolution of their VMA at 28 days, compared to 6.2% of the placebo group (p≡0.001). In subjects without epiretinal membrane, microplasmin was shown to be even more effective, with 34.5% seeing resolution at 28 days, compared to 6.4% of the placebo group. Additional endpoints were also reached. Microplasmin was also highly effective in treating full thickness macular hole and improving visual acuity, both without the need for vitrectomy. Microplasmin was generally safe and well tolerated.
March 29, 2010
Othera released positive results from a phase I/II trial of OT-551 for the treatment of bilateral geographic atrophy, an advanced form of dry age-related macular degeneration (AMD). This open label study enrolled ten subjects with advanced dry AMD in both eyes. All subjects received 0.45% OT-551 daily for 24 months in one eye, which was randomly chosen. The untreated fellow eye served as a control. The primary endpoint was mean change in best-corrected visual acuity (BCVA) at the end of 24 months. A statistically significant difference in favor of OT-551 was observed. The mean change in BCVA for the dosed eye was 0.2±13.3 letters gained versus 11.3±7.6 letters lost for fellow eye control (p≡.0295). No other meaningful differences between study eyes and fellow eyes were observed in other endpoints. There were no drug-related serious adverse events.
May 11, 2009
Ophthotech reported results from a phase I trial of E-10030 for the treatment of neovascular age-related macular degeneration. This open-label, single group assignment study was conducted in the US. The subjects received E-10030 as an intravitreous injection as a montherapy or in combination with ranibizumab 0.5 mg/eye. The primary endpoint was ophthalmic dose limiting toxicities. Of the subjects treated with E-10030, 59% gained significant vision (3-line gain) at week 12 after therapy. All (100%) of treated subjects demonstrated neovascular regression. E10030 was well tolerated with no evidence of drug-related adverse events.
April 20, 2009
Sirion Therapeutics reported positive interim results from a phase II trial of fenretinide for the treatment of geographic atrophy (GA) associated with age-related macular degeneration. The subjects enrolled in this randomized, double-masked, placebo controlled, dose-comparison trial were treated with daily doses of placebo or 100mg or 300mg of oral fenretinide. Data showed slower growth of the GA lesions for the 300mg dose for all lesion sizes at entry. This trend was observed at six months and increased over time. Among a sub-population of 78 subjects who reached the 18 month study visit, the median growth rate of the lesions in the 300mg group was 22.7% versus 41.6% in the placebo group, representing a 45% reduction in median lesion growth rate at month 18. Slower lesion growth was also observed in the 100mg group among subjects who had lesions smaller than the median baseline at entry (approximately 3 disk areas). Based on the results, this trial will continue as planned.
April 6, 2009
NeuroTech Pharmaceuticals released positive results from a phase II trial of NT-501 for the treatment of dry age-related macular degeneration (AMD) involving geographic atrophy (GA). This multi-centered, randomized, double-masked, sham-controlled study enrolled 52 subjects who received either a high or low dose NT-501 implant or a sham treatment in one eye only. They were subsequently measured for changes in best corrected visual acuity (BCVA) at 12-months. The high dose of NT-501 stabilized BCVA at 12-months, with 96.3% (p≡0.078) of treated subjects losing fewer than three lines of vision, or 15 letters, versus 75% of the subjects in the sham-treatment group. This trend in visual acuity stabilization at 12 months was preceded by a dose-dependent, statistically significant increase in retinal thickness (p<0.001 and p≡0.013 for high and low dose, respectively) that was observed as early as four months post-implantation.
April 2, 2007
Bayer and Regeneron announced positive preliminary results from aphase II trial of VEGF Trap-Eye for the treatment of AMD. This trial enrolled150 subjects who were randomized into five groups to receive either 0.5 or 2. 0mg of VEGF Trap-Eye administered every four weeks or a single dose of 0.5, 2. 0,or 4.0 mg of VEGF Trap-Eye. Subjects were then monitored for safety, retinalthickness and visual acuity over 12 weeks. These results are from the first 78subjects who have completed the 12 week treatment duration. Treatment wasgenerally well tolerated, with no drug-related serious adverse events. Theprimary endpoint was achieved, with a statistically significant reduction inretinal thickness compared to baseline (all groups combined, decrease of 135microns, p ≤ 0.0001). The secondary endpoint, mean change from baseline invisual acuity, was also met (all groups combined, increase of 5.9 letters, p ≤0.0001). In the subjects receiving the single dose statistical significance wasobserved, with a decrease in excess retinal thickness (p ≤ 0. 0001) and anincrease in visual acuity (p = 0.012) at 12 weeks compared to baseline. Basedon the results, Bayer and Regeneron plan to initiate a phase III trial of VEGFtrap in the second half of 2007.
February 5, 2007
Athenagen issued positive results from a phase I trial of ATG003 for the treatment of neovascular age-related macular degeneration (AMD). This randomized, double-masked, placebo-controlled trial enrolled 80 healthy subjects who received single and multiple ascending dose regimens by eye drop twice daily for up to 14 days. The primary endpoints, ocular and systemic safety, were achieved. The drop therapy showed excellent ocular tolerability and very low levels of the compound were found in the blood following administration, demonstrating an excellent systemic safety profile as well. Based on the results, Athenagen plans to initiate a phase II trial of ATG003 in Q1 2007 for the treatment of wet AMD.
August 14, 2006
Sirna Therapeutics reported positive results from a phase I trial of Sirna-027 for the treatment of age-related macular degeneration (AMD). This trial enrolled 26 subjects, with active disease, who received a single intravitreal injection of Sirna-027 in doses ranging from 100-1,600 mcg. Safety data revealed the drug to be safe and well tolerated for all subjects, across all dose levels. Efficacy data were positive, with 19% of the subjects displaying clinically significant improvement in visual acuity eight weeks after the initial, single injection. Three months after initial injection, 92% of the subjects showed visual acuity stabilization, with 15% experiencing clinically significant improvement in visual acuity. Based on these results Sirna, in collaboration with Allergan, Inc., expected to initiate phase II trials during the second half of 2006.
June 5, 2006
Acuity Pharmaceuticals issued positive results of their phase II C.A.R.E. trial of bevasiranib (Cand5), for the treatment of wet age-related macular degeneration (AMD), at the ASGT annual meeting. Top line data indicated a positive safety profile, with no serious adverse events reported and a positive overall tolerability profile. Preliminary response was noted in several measures, including near vision, lesion size (CNV) and time to rescue. All doses of the drug produced evidence of efficacy; the magnitude of response was seen to be dose related. This randomized, double-blind study enrolled 129 patients with serious disease across 28 sites in the US, who received one of 3 doses of the drug.
March 6, 2006
Genaera has issued positive interim results of their phase II "MSI-1256F-209" trial of Evizon (squalamine lactate) for the treatment of wet age-related macular degeneration (AMD). Results to date indicate that the 40 mg dose of the drug was safe and well tolerated, and stabilized or improved vision (a loss of >15 letters in visual acuity) in treated patient eyes in 83% of subjects, compared to 71% for placebo at 24 weeks. The effect was more pronounced in subjects not receiving background photodynamic therapy with verteporfin (83% for Evizon vs. 60% for placebo, respectively). Some benefits were also noted in patients' untreated eyes. This randomized, multi-center, double-masked, controlled study was designed to investigate the safety and efficacy of two doses of the drug (40 mg or 20 mg) compared to placebo in one patient eye, with the other eye remaining untreated as an in-subject baseline comparator. Based on these results, the company announced plans to initiate an additional phase II trial of the drug, dubbed MSI-1256F-212.
February 13, 2006
GenVec reported positive results of a phase I trial of their AdPEDF adenoviral-vector gene therapy for the treatment of wet AMD in the journal Human Gene Therapy. Single administrations of the drug were shown to prevent increases in retinal lesion size 6 and 12 months after treatment at higher doses; these doses also maintained visual acuity through 12 months (visual acuity deteriorated at both 6 and 12 months with lower doses of the drug). No serious adverse events were reported, and no there was no incidence of dose-limiting toxicity or ocular inflammation. This multi-center, open-label, dose-ranging study enrolled 28 patients, who received single administrations of the drug with a observational follow-up at 6 and 12 months.
Regeneron issued preliminary positive results of a phase I trial of VEGF trap, for the treatment of neovascular age-related macular degeneration (wet AMD). Optical coherence tomography indicated rapid onset, substantial reductions in retinal thickness through 4 weeks, offering preliminary evidence of efficacy. Treatment was well tolerated, with no incidence of ocular inflammation; maximum tolerated dose had not yet been reached. This open-label dose-escalation study had enrolled 18 wet AMD patients to date, who had received single doses of the drug up to 2 mg, with a 3 month observational follow-up. Dose escalation through 4 mg is ongoing.
January 23, 2006
Genentech has issued additional positive results of a phase III trial, dubbed ANCHOR, of Lucentis (ranibizumab) for the treatment of wet age-related macular degeneration (AMD). The company previously announced that a significantly greater portion of subjects lost fewer than 15 letters in visual acuity at 1 year, compared to approved treatment with Visudyne (94% for low dose and 96% for high dose Lucentis, vs. 64% for Visudyne; p<0.0001). New data indicated superior efficacy in maintaining or improving visual acuity at 1 year, compared to Visudyne (+8.5 letters and +11 letters, respectively, vs. -9.5 letters). This ongoing, randomized, two-year, multi-center, double-blind, active-treatment controlled study enrolled 423 wet AMD patients , who received one of two doses of Lucentis (0.3 mg or 0.5 mg) once monthly or Visudyne once every 3 months for 2 years.
GenVec announced positive results of a phase I trial of AdPEDF.11, an adeno-virus vector PEDF gene therapy for the treatment of wet AMD, in the journal Human Gene Therapy. Trial data yielded a positive safety profile, with no serious adverse events reported. 25% of patients experienced transient intraocular inflammation, but no severe inflammation was observed. No positive adenoviral cultures were noted. Preliminary data suggested efficacy in maintaining or improving visual acuity and lesion size at higher doses at 6 and 12 months. This multicenter, open label, dose escalation study enrolled 28 patients, who received one of 8 doses of the drug (10^6, 10^6.5, 10^7, 10^7.5, 10^8, 10^8.5, and 10^9 particle units, n=3 subjects at each dose; and 10^9.5 particle units, n=8), with 12 month follow-up.
November 14, 2005
Genetech issued positive interim results of their second phase III trial of Lucentis (ranibizumab), dubbed ANCHOR, for the treatment of age-related macular degeneration with choroidal neovascularization (wet AMD). Trial results met their primary efficacy endpoint, with 94% of patients in the low dose group and 96% in the high dose group experiencing maintained or improved vision on the ETDRS diagnostic chart, compared to 64% of subjects completed with verteporfin photodynamic therapy (PDT) during the first year (p<0.0001). Secondary efficacy was also established, with Lucentis subjects experiencing a mean increase in visual acuity at 1 year, compared to a mean decrease for PDT subjects (p<0.05). This randomized, multi-center, double-masked, active-treatment controlled study enrolled 23 patients with predominantly classic wet AMD, who were randomized 2:1 to receive one of two doses of Lucentis (0.3 mg or 0.5 mg) via intravitreal injection once monthly or PDT every three months for 2 years. These data, in combination with results from the company's other phase III study MARINA, were to be included in the company's upcoming BLA filing, planned for December 2005.
October 17, 2005
Genaera announced preliminary results of a phase II trial of Evizon (squalmine lactate), for the treatment of wet age-related macular degeneration (wet AMD). Primary safety data were considered positive, and efficacy was demonstrated in a number of secondary measures. Specifically, subjects receiving 40 mg Evizon plus photodynamic therapy (PDT) achieved a small improvement in visual acuity from baseline at 29 weeks, compared to a decrease in acuity for subjects receiving PDT alone, and only 10% of subjects receiving the drug required a second course of PDT, compared to 47% of subjects receiving PDT alone. This multi-center, randomized, controlled, masked study enrolled 45 wet AMD patients, who received one of three doses of Evizon (10 mg, 20 mg or 40 mg; n=10 subjects per cohort) in combination with PDT, or PDT alone (n=15).
June 6, 2005
Genentech and Novartis have reported positive results of their phase I/II "FOCUS" trial of Lucentis (ranibizumab) in combination with verteporfin photodynamic therapy (PDT) for the treatment of wet age related macular degeneration (AMD). Trial data indicated that the combination therapy yielded maintained or improved vision (defined as a loss of 15 letters or less) in 90% of subjects, vs. 68% in subjects receiving PDT alone (p<0.0003). Secondary efficacy was noted in mean visual acuity at 12 months, with subjects receiving the combination experiencing a significant improvement in acuity, compared to a mean decreased in PDT subjects. Serious adverse events, including uveitis, endophthalmitis, and cerebral vascular events, occurred more frequently with Lucentis than PDT alone, while myocardial infarctions occurred less frequently. This single-blind study enrolled 162 wet AMD patients across 25 US sites, who were randomized 2:1 to receive either 0.5 mg Lucentis or sham injections for 23 months, following PDT therapy.
May 30, 2005
Genentech reported positive results of a phase III trial of Lucentis (ranibizumab), their anti-VEGF antibody under investigation for the treatment of "wet" age-related macular degeneration (AMD). Trial data met their primary efficacy endpoint, with 95% of patients experiencing maintained or improved visual acuity at 1 year, vs. 62% of subjects in the control group (p<0.0001). Furthemore, subjects receiving the drug experienced significant mean improvement in visual acuity, compared to a mean decrease in visual acuity for the control group. Overall adverse events were generally mild to moderate, though infrequent incidence of serious adverse events was noted in the Lucentis group, including uveitis and endophthalmitis. This randomized, double-blind trial enrolled a total of 716 subjects in the US, who received intravitreal injections of one of two doses of Lucentis (0.3 or 0.5 mg) or sham treatment (local anesthetic but no injection) once monthly for 2 years. Genentech announced plans to present full one-year data at the 23rd Annual Meeting of the American Society of Retina Specialists in July.
May 9, 2005
Genaera issued interim results of a phase II trial, dubbed MSI-1256F-208, of Evizon (squalamine lactate) for the treatment of wet age-related macular degeneration (AMD). 9-week data from the ongoing study yielded evidence of efficacy, with Evizon producing a mean gain from baseline of 1.3 EDTRS letters (range +16 to -17; n=24) in visual acuity, vs. a loss of 0.9 EDTRS letters (range +15 to -19; n= 15) for placebo. This ongoing, randomized, double- blind, placebo-controlled, multi-center study has enrolled 46 subjects across 15 US sites, who continue to receive monthly infusions of Evizon or placebo, in combination with photodynamic therapy with vertepofin (PDT) at week 3, with optional additional PDT at weeks 15 and 27 based on need. The treatment period is scheduled to last through week 25, with a 1 year observational follow-up scheduled thereafter.
Neurotech SA issued positive results of a phase I trial, dubbed 03-EI-0234, of NT-501, their investigational ciliary neurotrophic factor (CNTF) delivery vector based on their Encapsulated Cell Technology platform, for the treatment of retinitis pigmentosa (RP). Primary safety endpoints were achieved, with no reported serious adverse events and a positive overall tolerability profile. Preliminary efficacy was also noted, with some patients experiencing a one-line-or-greater improvement in visual acuity. This open-label study enrolled 10 patients with late stage RP, who received intravitreal implantation of NT-501 ECT cells at one of two dose levels (5-fold difference between doses). The company announced plans to initiate a multi- center phase II trial of the drug in the near future, based on these results.
Regeneron reported positive results of a phase I trial of systemically-administered Vascular Endothelial Growth Factor (VEGF) Trap, for the treatment of wet age-related macular degeneration (AMD). Preliminary trial data indicated that the drug produced a significant decrease in excess retinal thickness, vs. placebo. This effect was seen to be dose dependent in both magnitude and duration. The drug also produced a dose-dependent increase in blood pressure, a commonly observed effect of systemically administered anti-VEGF agents. This randomized, double-blind, placebo-controlled, ascending dose study enrolled 25 subjects, who received one of three doses of systemic VEGF Trap (0.3 mg/kg, 1.0 mg/kg or 3.0 mg/kg) or placebo. Based on these results, the company announced plans to initiate a phase I trial in mid-2005 to investigate intravitreal injections of VEGF Trap, in hopes of limiting systemic hypertension.
Sirna Therapeutics reported positive results of a phase I trial of Sirna-027, their short interfering RNA (siRNA) treatment for the treatment of wet AMD. Interim results from the study met primary safety and tolerability endpoints, with no drug-related systemic or local adverse events noted. Dose-limiting toxicity/ maximum tolerated dose had not yet been reached. Preliminary evidence of efficacy, including stabilization of visual acuity in all patients for the duration of treatment, was observed. This open- label dose-escalation study had enrolled and treated 14 of 30 planned subjects across 4 US sites to date, with single intravitreal doses ranging from 100-800 mcg. The company announced plans to initiate phase II trials, pending final positive analysis of the data set.
March 7, 2005
Genaera reported positive preliminary result of a phase II trial of Evizon (squalamine lactate), their intravenous anti-angiogenic compound under development for the treatment of wet age-related macular degeneration (AMD). Pharmacokinetic data indicated no changes in absorption, metabolism, elimination or accumulation over 5 weeks of treatment, and yielded an elimination half-life of roughly 7 hours. Furthermore, all patients receiving the higher dose of the drug demonstrated maintained or improved vision at 3 weeks (2 doses) and 5 weeks (4 doses, end of treatment), and at 2 and 4 month follow-ups; 90% of eyes at the lower trial dose experienced maintained or improved vision at 4 months. No serious adverse events were observed, though one patient in the low dose group withdrew after lack of efficacy. This preliminary data concerned 12 patients with confirmed wet age-related macular degeneration (AMD), who were randomized to receive 4 weekly treatments with either low-dose (10 mg.) or high-dose (40 mg.) Evizon. Treatment and data collection from this ongoing study continue; the company announced that full enrollment of 45 patients was recently completed, and they were also beginning to plan phase III trials.
January 18, 2005
Genaera reported positive preliminary data from an ongoing phase II trial of their anti-angiogenic drug squalamine for the treatment of choroidal neovascularization in “wet” age-related macular degeneration (AMD). Results from 6 patients treated with squalamine thus far demonstrated notable efficacy, with 100% of eyes (n=12) having preserved or improved vision after two doses of squalamine (3 weeks), end of therapy at 5 weeks, and at a two month follow-up. Furthermore, no withdrawals from therapy or drug-related serious adverse events have been noted to date. Subjects in this open-label study received four weekly doses of 40 mg. squalamine without additional therapy, and were followed through 2 months from trial initiation. Genaera announced that data from this trial are to be presented at the 28th Annual Meeting of the Macula Society in February 2005, and, pending successful completion of this and two other phase II trials currently ongoing, they expected to initiate a phase III study of the drug later this year.
November 1, 2004
GenVec reported positive results of a phase I trial of AdPEDF in patients with wet age-related macular degeneration (AMD) at the Subspecialty Retina Day symposium of the first joint session of the American Academy of Ophthalmology and the European Ophthalmology Society. Trial data met the primary safety and tolerability endpoints, with no dose-limiting toxicities, serious adverse events, or treatment-related infections. Secondary evidence of efficacy was also noted, with observed improvements in appearance of retinal health and stabilization of visual acuity. This open-label, dose escalating study enrolled 28 AMD patients into one of 8 dosing cohorts across six US sites. GenVec announced plans to investigate the drug in patients with less severe AMD to investigate efficacy.
ISTA Pharmaceuticals presented combined the results of a pair of phase III trials of Xibrom (bromefac sodium ophthalmic solution), for the treatment of ocular inflammation, eye pain and photosensitivity following cataract surgery. The combined data from the two trials (both conducted under the same protocol) indicated that a significantly larger portion of patients treated with Xibrom met the primary efficacy endpoint compared with placebo, as measured by the incidence of patients with complete absence of ocular inflammation at the end of the dosing period (64% vs. 40%; p<0.0001). Additional evidence of rapid, three day efficacy was also observed, and the Xibrom group experienced a lower incidence of adverse events than the placebo group. The randomized, double-blind, placebo-controlled studies enrolled a total of 527 subjects across 39 US sites, who received either topical Xibrom or placebo twice daily for 14 days, following surgical cataract removal.
Lilly has issued the results of a pair of analyses of two phase III trials of their investigational compound ruboxistaurin, for the treatment of diabetic macular edema (DME). Combined trial data indicated that the drug was efficacious in treating DME, promoting better visual acuity compared with subjects with similar degrees of macular damage receiving placebo, as measured by the number of correctly identified letters (71 vs. 60, p<0.01). In addition, a trend towards reduced DME progression was observed in subjects with significant degeneration near but not directly involving the macula, compared with placebo (20% vs. 31%, p=0.083). Both phase III trials were double-blind, long term investigations (30 and 36 month minimum durations), and enrolled more than 900 patients with DME. Lilly announced that these analyses would be used to support an ongoing phase III trial of the drug.
October 18, 2004
Alcon has issued one-year results of a phase III approved-therapy-comparison study of Retaane (anecortave acetate), their investigational angiogenesis inhibitor for the treatment of wet age-related macular degeneration (AMD). Trial data demonstrated that the drug did not meet the trial’s primary non-inferiority endpoint, with 45% of subjects receiving Retaane maintaining vision, compared to 49% receiving approved Visudyne photodynamic therapy, as measured by less-than three line losses in visual acuity from individual baseline. This difference, however, was non-significant, and Alcon announced that they had preliminary indications that slight administration protocol modifications might produce moderate improvements in patient outcomes. Secondary safety endpoints were successfully reached, with no serious adverse events associated with either the drug or administration procedure. This ongoing, multi-center, phase III clinical trial enrolled 530 patients with AMD, who were randomized to receive either Retaane via posterior juxtascleral depot administration (dosing by blunt cannula inserted behind the eye) or Visudyne therapy (intravitreal injection plus photodynamic therapy). Alcon announced that they planned to submit these data to the FDA, as part of their rolling NDA filed in 2003.
May 10, 2004
GenVec reported interim positive results from a phase I trial investigating AdPEDF, an angiogenesis inhibitor for the treatment of wet age-related macular degeneration (AMD). Results demonstrated that AdPEDF was well tolerated at all dose levels with no ocular inflammation or endophthalmitis reported. Positive changes in visual acuity and retinal appearance were also observed. No dose limiting toxicities or drug related serious adverse events have been observed. The ongoing, multi-center, dose escalation study has enrolled 24 subjects to date with AMD who were administered a single intravitreal injection of AdPEDF. Results were reported at the Annual Meeting of the Association for Research in Vision and Ophthalmology in Ft. Lauderdale.
December 1, 2003
ISTA Pharmaceuticals reported positive results from two-phase III trials investigating Vitrase (ovine hyaluronidase) for the treatment of vitreous hemorrhage. Results demonstrated a statistically significant reduction in vitreous hemorrhage density as early as one month through three months after Vitrase injection compared to injection of saline solution. Treatment with Vitrase showed improvement in best-corrected visual acuity of three or more lines on an eye chart compared to saline solution. In addition, the density of the vitreous hemorrhages showed a significant decrease compared to placebo. The randomized, double-blind, placebo-controlled studies enrolled 1,306 subjects at sites worldwide. Results were reported at the Annual Meeting of the American Academy of Ophthalmology in Anaheim.
Miravant Medical Technologies reported positive results from two-phase III trials investigating SnET2, a photodynamic therapy for the treatment of wet age-related macular degeneration (AMD). Results showed that SnET2 (0.5mg /kg) stabilized visual acuity in a statistically significant number of subjects compared with placebo. Data showed that subjects who received three treatments over the first six months benefited most. The two randomized, placebo-controlled, parallel group studies enrolled a total of 920 subjects at 60 U.S. sites. Subjects received placebo or one of two drug doses tested. Visual acuity was measured using the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart and compared to baseline. The results were reported at the American Academy of Ophthalmology in Anaheim.
September 15, 2003
Genaera reported positive preliminary results from a phase I/II trial investigating squalamine, an anti-angiogenic for the treatment of choroidal neovascularization with AMD (wet AMD). Results showed 97% of subjects treated with squalamine had preserved or improved vision two months after initiation of therapy. Thirteen subjects (33%) had three lines or greater improvement in visual acuity, and 25 subjects (64%) had preserved vision. Treatment consisted of four weekly doses of squalamine, with no further maintenance therapy, and follow up evaluations at two and four months. No withdrawals from therapy or drug related serious adverse events have been reported. Additional data is anticipated to be available later in 2003.
August 25, 2003
Genentech reported positive preliminary results from a phase Ib/II trial investigating Lucentis (rhuFab V2, ranibizumab), a humanized antibody for the treatment of age-related macular degeneration (AMD). Results showed that the visual acuity at Day 98 in subjects who continued with treatment improved by an average of 7.4 letters in the 300 ug group and 12.6 letters in the 500 ug group. In addition, subjects who received usual care demonstrated an average loss in visual acuity of 5.1 letters at Day 98. The randomized, open-label, single-agent study enrolled 64 subjects with minimally classic and predominantly classic wet AMD. Subjects were treated every four weeks for four doses (300-500 ug) of Lucentis or with usual care of observation or photodynamic therapy. Results were reported at The 21st Annual Meeting of the American Society of Retina Specialists in New York City.
May 19, 2003
Genaera reported positive early results from a phase I/II trial investigating squalamine, an anti-angiogenic drug for the treatment of age-related macular degeneration (AMD). Early results demonstrated shrinkage in the size of choroidal neovascularization lesions and stabilization of the lesions in some subjects. In addition, early trends for visual acuity showed some improvement in more than three lines of vision. The primary endpoint measures are visual acuity, ocular angiography and fundus photography. No serious adverse events or withdrawals from therapy have occurred in the trial to date. Squalamine is administered intravenously at doses of 25 or 50 mg/m2, once weekly for 4 weeks. The study is enrolling 40 subjects with AMD and is being conducted in Mexico City.
May 12, 2003
Oculex Pharmaceuticals reported positive results from a phase II trial investigating Posurdex, a dexamethasone releasing implant for macular edema. Results showed that after 90 days of receiving Posurdex, subjects experienced a statistically significant improvement in visual acuity compared with subjects receiving no treatment, as measured on a standard eye chart. Data showed that measures of edema demonstrated statistically significant decreases in both retinal thickness and fluorescein leakage. The randomized, multi-center, dose ranging study enrolled 306 subjects who received either a single Posurdex implant containing dexamethasone, or no treatment. The primary efficacy endpoint was to determine whether Posurdex could provide a two-line or greater improvement in visual acuity. Posurdex displayed a positive safety profile with only 4% of subjects experiencing a mild rise in intraocular pressure following treatment.
QLT and Novartis Ophthalmics reported positive results from a phase IV trial investigating Visudyne (verteporfin), a photodynamic therapy for the treatment of choroidal neovascularization. Results suggested that subjects with minimally classic lesions who were treated with Visudyne therapy had a reduced risk of vision loss compared with placebo-treated subjects. Data showed that the mean change in visual acuity scores for Visudyne treated subjects was higher in each group compared with subjects given placebo. The trial also demonstrated that fewer Visudyne-treated subjects developed predominantly classic choroidal neovascularization compared with placebo. The 12-month, multi-center study enrolled 117 subjects with choroidal neovascularization due to age-related macular degeneration. The data confirms six-month trial results presented earlier this year at the Macula Society annual meeting.
October 7, 2002
Alcon's ongoing study of wet age-related macular degeneration (AMD) demonstrated that 15 mg anecortave acetate was significantly superior compared to placebo at preserving vision, preventing severe vision loss and inhibiting lesion growth in the retina. The results showed that 79% of subjects treated with 15 mg anecortave acetate lost fewer than three lines of vision from baseline at the month 12 visit, compared to 53% of placebo subjects. In the sub-group of subjects with predominantly classic lesions, which are more severe, 84% of anecortave acetate treated subjects lost fewer than three lines of vision compared to 50% of placebo subjects.
June 10, 2002
Bausch & Lomb and Control Delivery Systems reported positive results from a phase III trial testing an ophthalmic implant based on Envision TD technology. The implant is designed to deliver fluocinolone acetonide directly to the affected area of the eye for up to three years. Results of an intent-to-treat analysis showed that subjects receiving the implant (versus standard of care) experienced a statistically significant reduction in macular edema. Treatment with the implant also reduced the severity of diabetic retinopathy, and over 80% of subjects had improved or stable visual acuity, compared to 50% treated with standard of care.